In recent years, with a people's growing interest in nature, as for fragrances, those of high preference, which characteristically evoke the image of natural environment, are attracting attention.
Musk is a product obtained by drying the secretion of the musk gland of male musk deer, and has been highly valued since ancient times, as a fragrance or as a natural medicine. Musks having strong scent have been considered as good products, but today, products containing 2% or more of muscone are considered as better products. Musk deer is an animal of family Moschidae, inhabiting a region extending from the mountainous area in Himalaya to the inland China, and currently importation and exportation of the animal is banned under the Washington Convention. Accordingly, only natural musk that was imported prior to the Washington Convention can be used, and unless artificial breeding of musk deer is achieved successfully, natural musk cannot be put into use in the future.
3-Methylcyclopentadecanone (hereinafter, may be referred to as muscone), which is an ingredient of musk, is one species of typical musk-based fragrances, and it is known that there are differences in the scents depending on the configuration of the methyl group. The optically active isomers of muscone, the (R)-(−)-isomer and the (S)-(+)-isomer, are both useful as fragrances, but the (R)-(−)-isomer has stronger and richer scent compared to the (S)-(+)-isomer. For example, while the (S)-(+)-isomer has a threshold value of 223 ppb, the (R)-(−)-isomer has a threshold value of 61 ppb, and thus the (R)-(−)-isomer is reported to be superior (see Non-Patent Document 1).
From the aspect of activity as well as from the aspects of a growing interest in nature and environment, the interest in (R)-isomers which are excellent in biodegradability is growing, and there has been a demand not for racemates, but for optically active isomers. Furthermore, a number of methods for the optical resolution of racemates have been studied (see, for example, Patent Document 1), but in this method, generation of (S)-isomers is unavoidable. Therefore, a study of the method for selectively producing the (R)-isomer of muscone has been extensively carried out. A method of producing the (R)-isomer using an optically active raw material (see, for example, Patent Document 2), a method of subjecting 3-methyl-2-cyclopentadecen-1-one to asymmetric hydrogenation (see Patent Document 3), and the like have been developed. Then, alkylation resulting from 1,4-addition reaction of α,β-unsaturated ketone by an alkylating agent such as dimethylzinc has been reported (see Patent Document 4), and attention has been focused on the methylation of 2-cyclopentadecen-1-one. In recent years, there have been reports on the method for stereoselective production of muscone of the (R)-isomer through a reaction of 1,4-conjugate addition of a methyl group with respect to 2-cyclopentadecen-1-one. As an example of the method, it has been reported that favorable results can be obtained by using a chiral auxiliary having a bornane skeleton during the synthesis (Non-Patent Document 2). Further, as another example, methods of using various phosphite compounds as ligand are also known (Non-Patent Document 3). In addition to these examples, there are reports on the production of optically active muscone using a complex of copper and a ligand such as mesomer-derived 4-(cis-2,6-dimethylpiperidine)-(R)-dinaphthodioxaphosphepine (Patent Document 5), synthesis of (R)-muscone in which asymmetric methylation by means of dimethylzinc is performed by making use of deoxycholic acid, and a phosphite compound having a binaphthyl group as the chiral base, as optically active ligands, and combining these with a copper catalyst (Non-patent Document 4), and the like.
Moreover, under such circumstances, new methods for the preparation of the raw material, 2-cyclopentadecen-1-one have also been developed (see Patent Document 6).
[Patent Document 1] Japanese Patent Application Laid-open No. 2005-8555
[Patent Document 2] Japanese Patent Application Laid-open No. 2002-30022
[Patent Document 3] Japanese Patent Application Laid-open No. 6-192161
[Patent Document 4] Japanese Patent Application National Publication No. 2001-316309
[Patent Document 5] Korean Patent Application Laid-open No. 2000-49811
[Patent Document 6] Japanese Patent Application National Publication No. 2001-226306
[Non-Patent Document 1] W. Pickenhagen et al., ACS SYMPOSIUM SER. 388 Flavor Chemistry, 1989, p. 151
[Non-Patent Document 2] J. Chem. Soc. Perkin Trans. I, 1193, (1992)
[Non-Patent Document 3] Synlett, 1999, No. 11, 1181
[Non-Patent Document 4] Tetrahedron: Asymmetry, 15 (2004) 2533